1-153537303-T-C

Variant names:

• chr1-153537303-T-C
• NM_001394232.1:c.272A>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001394232.1(S100A5):​c.272A>G​(p.Asn91Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,386 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: S100A5 NM_001394232.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.576
• Publications: 0 publications found

Genes affected

S100A5 (HGNC:10495): (S100 calcium binding protein A5) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21. This protein has a Ca2+ affinity 20- to 100-fold higher than the other S100 proteins studied under identical conditions. This protein also binds Zn2+ and Cu2+, and Cu2+ strongly which impairs the binding of Ca2+. This protein is expressed in very restricted regions of the adult brain. [provided by RefSeq, Jul 2008]

ENSG00000238279 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03278327).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394232.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A5	NM_001394232.1	MANE Select	c.272A>G	p.Asn91Ser	missense	Exon 3 of 3	NP_001381161.1	P33763-1
	S100A5	NM_001394233.1		c.272A>G	p.Asn91Ser	missense	Exon 2 of 2	NP_001381162.1	P33763-1
	S100A5	NM_001394234.1		c.272A>G	p.Asn91Ser	missense	Exon 3 of 3	NP_001381163.1	P33763-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A5	ENST00000368717.3	TSL:3 MANE Select	c.272A>G	p.Asn91Ser	missense	Exon 3 of 3	ENSP00000357706.2	P33763-1
	S100A5	ENST00000368718.5	TSL:1	c.272A>G	p.Asn91Ser	missense	Exon 4 of 4	ENSP00000357707.1	P33763-1
	S100A5	ENST00000963779.1		c.272A>G	p.Asn91Ser	missense	Exon 2 of 2	ENSP00000633838.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461386 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726914

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.0000447 AC: 2 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5760

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111652

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.040
DANN	Benign	0.47
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-0.94	T
PhyloP100		-0.58
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.025
Sift	Benign	1.0	T
Sift4G	Benign	0.74	T
Vest4		0.025
MutPred		0.22		Gain of glycosylation at N91 (P = 0.0484)
MVP		0.13
MPC		0.010
ClinPred		0.019	T
GERP RS		-2.1
Varity_R		0.13
gMVP		0.073
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr1-153509779;